Serotonergic abnormalities have long been associated with autism, as has interest in serotonergic mechanisms in the manifestation of affective disturbance. In spite of their widespread use, there are no controlled clinical trials of any serotonin reuptake inhibitors (SRIs) in children with autism to support this practice. Citalopram is the newest of the SRIs to become available in the U.S., and offers some potential pharmacokinetic advantages over the other drugs in its class. We propose to study the treatment of affective disturbance in children with autism through experiments addressing three specific aims: Aim I. To determine if the serotonin reuptake inhibitor, citalopram, is effective in the treatment of behavioral disturbance in children with autism. Aim II.To determine if physiological or genetic markers, measures of family function, or particular pretreatment symptoms are predictive of sensitivity and response to treatment with citalopram. Aim Ill. To better understand the response in clinical trials of children with autism by identifying factors influencing parent and clinician ratings of change and to develop new strategies by which to capture the response to therapeutic interventions. Beyond a clinical trial, then, this project will study how best to capture meaningful treatment response in children with autism. Recent experience with clinical trials in this population suggests that current assessment strategies can be improved. Current measures may be susceptible to nonspecific influences that show up as placebo effects. Likewise, important clinical improvement may go uncaptured or be diluted with assessment instruments currently employed. This proposal integrates data from the other projects in the Center, and will set the stage for the Center's role not only to advance knowledge of autism through important research, but to be an ongoing resource to children and families through education and treatment. By formally studying current treatment and by developing new assessment strategies and improving regional accessibility for evaluation and treatment of children with autism, the Center will be positioned to efficiently collaborate with other Centers in the network, and will be a pivotal resource to UDDer New Enaland.